Electrical properties of bimolecular lipid membranes (BLM) are measured to study: (1) mechanisms of transport of ions mediated by carriers or channels; (2) properties of ionophores isolated from natural cell membranes; (3) mechanisms of immune cytotoxicity; (4) the effect of the membrane potential on the disposition of membrane proteins. A solubilized detergent-free preparation of the hepatic binding protein for asialoglycoproteins associates spontaneously with small, unilamellar lipid vesicles. In a BLM it induces voltage-dependent increases in ion conductance across the bilayer probably reflecting penetration of the protein into the bilayer towards an electrically positive pole. In the presence of specific ligand this penetration leads to translocation of the receptor from one side of the bilayer to the other. These observations suggest a mechanism by which biological membranes might regulate the disposition of their proteins and a way which membrane receptors involved in endocytosis might be spared lysosomal destruction in order to be recycled to the plasma membrane.